Adenovirus type 5-expressing Gn induces better protective immunity than Gc against SFTSV infection in mice.

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-10-19 DOI:10.1038/s41541-024-00993-y
Hua Qian, Li Tian, Wenkai Liu, Lele Liu, Menghua Li, Zhongxin Zhao, Xiaoying Lei, Wenwen Zheng, Zhongpeng Zhao, Xuexing Zheng
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Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development.

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表达 Gn 的腺病毒 5 型能比 Gc 更好地诱导小鼠对 SFTSV 感染的保护性免疫。
严重发热伴血小板减少综合征(SFTS)是由 SFTS 病毒(SFTSV)引起的,发病率和死亡率都很高。SFTSV 表面糖蛋白(G)的主要免疫优势区仍不清楚。在本研究中,我们构建了表达 SFTSV G 不同区域(Gn、Gc 和 Gn-Gc)的 5 型腺病毒(Ad5)载体候选疫苗,并评估了它们在小鼠中的免疫原性和保护效力。在野生型小鼠中,与 Ad5-Gc 或 Ad5-Gn-Gc 相比,Ad5-Gn 在淋巴结或外周血中招募/激活了更多树突状细胞和 B 细胞,在脾细胞中引起 Th1/Th2 介导的反应,并触发了更高水平的 SFTSV 中和抗体。在 IFNAR Ab 处理的小鼠中,免疫 Ad5-Gn 比 Ad5-Gc 或 Ad5-Gn-Gc 对 SFTSV 挑战有更好的保护作用。此外,被动免疫显示 Gn 特异性血清而非 Gc 具有完全的保护性免疫力。总之,我们的数据表明,Gn 是 SFTSV G 的免疫优势片段,可以作为 SFTSV 疫苗开发的潜在候选片段。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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